Methods and Systems for Dosing a Medicament

ABSTRACT

A manually actuated pump, such as a bolus delivery circuit of an insulin pump, combines a direct drive piston system with a lost motion valve system, to deliver reliably a full bolus dose, while precluding partial dosing or inadvertent overdosing conditions. The pump may also include a signaling device to indicate when a full bolus dose is delivered.

FIELD OF THE INVENTION

This invention relates generally to medicament delivery devices and,more specifically, to systems and methods for delivering a single bolusdose when activated by a user.

BACKGROUND

Medicament infusion devices are utilized to deliver liquid fluidmedicine to patients. For example, insulin infusion devices are oftenused by persons with diabetes to maintain adequate insulin levelsthroughout the day or to increase insulin levels during mealtime. Theseinsulin infusion devices can replace the syringe-based injections commonamong those with diabetes.

Insulin infusion devices are available in several forms and includeseveral common components. Generally, an infusion device includes ahousing that may be worn on a patient's clothing (a belt, for example)or on the patient himself, and that contains a number of mechanical andelectrical components. A reservoir holds the insulin and anelectro-mechanical pump mechanism (various types are used) delivers theinsulin as needed to the patient. Battery-powered electronics controlthe pump and ensure that the device is operating properly. Varioussensors communicate with the electronics and other components to detectocclusions, sound alarms, measure remaining insulin capacity, etc.

While these devices are useful, they do suffer from severalshortcomings. First, the high expense of the devices makes themaccessible to fewer people than the diabetic population members who maybenefit from their use. Second, failure or malfunction of one componentrequires repair or replacement of the entire device, a costly scenario.For example. If the pump fails, often the entire unit (including theproperly functioning—and expensive—electronics) must be replaced. Third,over time the device gets dirty due to repeated uses, which requiresperiodic cleaning and may cause a failure condition at a later date.Fourth, the complexity of the devices requires significant battery powerto operate pumps, monitor sensors, and send alerts and notifications toa patient. Power and electronic requirements are often so significant asto require large batteries, thus increasing the physical size, weight,and cost of the device. Fifth, in devices which administer a liquidfluid medicine on demand, a full dose may not always be delivered.

It is therefore desirable to ensure the delivery of a single, full doseof medicament with a low-cost, mechanical mechanism in a reliable andsafe manner.

SUMMARY OF THE INVENTION

In one aspect, the invention relates to a method of dosing a medicamentusing a mechanical pump system including an actuation element, a directdrive piston system including a piston, and a lost motion valve system.The method includes the steps of moving the actuation element from arest position to a fill end position to fill incrementally a pistonchamber of the piston system with medicament from a reservoir, movingthe actuation element an additional distance to a point of no return tomove a valve of the valve system from a fill position to a dosingposition, and moving the actuation element past the point of no returnto force a full dose of medicament out of the piston chamber to a dosingconduit.

In one embodiment of the above aspect, moving the actuation element fromthe rest position to the fill end position retracts the piston relativeto the piston chamber. In another embodiment, the direct drive pistonsystem includes a rack and gear system or a cam and follower system. Thedirect drive piston system may include both the rack and gear system andthe cam and follower system. In another embodiment, moving the actuationelement from the rest position to the fill end position does not movethe valve. In yet another embodiment, when the actuation element ismoved past the point of no return, the piston is decoupled from theactuation element and automatically delivers a full dose of medicamentto the dosing conduit.

In another embodiment of the above aspect, the method includes returningthe actuation element to the rest position after dosing to reset themechanical pump system. The actuation element may be returned to thetest position automatically and may pass through a reengagement positionprior to reaching the rest position. In one embodiment, cycling theactuation element from past the point of no return to a positionintermediate with the reengagement position delivers no additionalmedicament. In another embodiment, cycling the actuation element betweenthe rest position and a position before the point of no return deliversno medicament. The actuation element may exert a first increasingreaction force against an actuating force when filling the pistonchamber to the fill end position and a second lower reaction force whenthe actuation element moves past the fill end position.

In yet another embodiment of the above aspect, the valve may be movedfrom the dosing position to the fill position by the actuation element.The valve may allow fluidic communication between the reservoir and thepiston chamber only when the valve is in the fill position, and thevalve may allow fluidic communication between the piston chamber and thedosing conduit only when the valve is in the dosing position. The pistonsystem and the valve system may be configured to preclude direct fluidiccommunication from the reservoir to the dosing conduit. The reservoirmay hold a first volume of medicament less than a volume of areplenishment reservoir. In further embodiments, the valve systemincludes a redundant sealing system having two sealing elements disposedbetween the reservoir and the dosing conduit and a venting port disposedbetween the two sealing elements for dumping medicament leaked betweenme two sealing elements. The piston system and the valve system maypreclude delivery of a partial dose of medicament to the dosing conduit.The mechanical pump system may also include an interlock for retainingthe valve in the dosing position until a full dose of medicament isdelivered.

In another embodiment of the above aspect, the method includesdelivering a signal only when the full dose is delivered to the dosingcircuit. The signal may be triggered by a mechanical, an optical, acapacitive, a potentiometric, or a magnetic input. The signal may betriggered based on detecting a specific position, a change in position,a threshold velocity, or a change in velocity of a moving component ofthe mechanical pump system. The signal may be a tactile stimulus, anaudible stimulus, a visual stimulus, an electronically detectable signaladapted to be received by an electronic device, or combinations thereof.

In another aspect, the invention relates to a mechanical pump systemincluding an actuation element and a direct drive piston systemincluding a piston chamber, a piston disposed within the piston chamber,and a direct drive coupled to the actuation element for moving thepiston relative to the piston chamber when the actuation element movesfrom a rest position to a fill end position to fill incrementally thepiston chamber with medicament. The mechanical pump system also includesa lost motion valve system including a valve chamber and a valvedisposed within the valve chamber. The valve is displaced from a fillposition to a dosing position after the actuation element travels beyondthe fill end position.

In one embodiment of the above aspect, the actuation element is amanually operable button. The actuation element may form a gap with thevalve so the valve does not move when the actuation element moves fromthe rest position to the fill end position. The actuation element maycontact the valve when the actuation element is beyond the fill endposition. In another embodiment, the mechanical pump includes a returnspring for biasing the actuation element toward the rest position. Thepiston chamber may contain a full dose of medicament when the actuationelement is at the fill end position to preclude delivery of a partialdose of medicament to a dosing conduit. The mechanical pump system mayinclude an interlock for retaining the valve in the dosing positionuntil a full dose of medicament is delivered. Moving the actuationelement from the rest position to the fill end position may compress apiston spring and an actuation element return spring, resulting in afirst increasing reaction force, and moving the actuation element pastthe fill end position toward the point of no return compresses furthersolely the return spring. The piston spring may be substantially fullyreacted by a cam disk when the actuation element reaches a point beyondthe fill end position, resulting in a decrease in force required to movethe actuation element toward the point of no return.

In another embodiment of the above aspect, the direct drive includes arack and gear system or a cam and follower system. The direct drive mayinclude both the rack and gear system and the cam and follower system.The cam and follower system may include a cam disk with a track forconstraining motion of a piston bar coupled to the piston. The track mayinclude a point corresponding to a point of no return of the actuationelement beyond which the piston becomes decoupled from the actuationelement. In yet another embodiment, the direct drive includes a ratchetelement mating with the cam disk to decouple the actuation element fromthe piston. The mechanical pump system may include a piston spring forbiasing the piston to empty the piston chamber when the piston isdecoupled from the actuation element. The cam disk may include a ledgefor mating with the ratchet element to recouple the actuation element tothe piston at a reengagement position. In other embodiments, the ratchetelement and the cam disk may be configured so that cycling of theactuation element from past the point of no return to a positionintermediate with the reengagement position fails to deliver medicamentthrough the valve, and the actuation element and the cam disk may beconfigured so that cycling of the actuation element between the restposition and a position before the point of no return delivers nomedicament.

In yet another embodiment of the above aspect, the valve fluidicallycouples a reservoir and the piston chamber only when the valve is in thefill position. The reservoir may hold a first volume of medicament lessthan a volume of a replenishment reservoir. The valve may fluidicallycouple the piston chamber and a dosing conduit only when the valve is inthe dosing position and the valve system may preclude direct fluidiccommunication between a reservoir and a dosing conduit. The valve systemmay include a fluidic outlet for dumping medicament if pressure exceedsa predetermined limit.

In one embodiment of the above aspect, the mechanical pump systemincludes a signaling device for delivering a signal as a full dose ofmedicament is delivered. The signaling device may be triggered by amechanical, an optical, a capacitive, a potentiometric, or a magneticinput. The signaling device may be triggered when a specific position, achange in position, a threshold velocity, or a change in velocity of amoving component of the mechanical pump system is detected. Thesignaling device may provide a tactile stimulus, an audible stimulus, avisual stimulus, an electronically detectable signal adapted to bereceived by an electronic device, or combinations thereof.

BRIEF DESCRIPTION OF THE FIGURES

Other features and advantages of the present invention, as well as theinvention itself, can be more fully understood from the followingdescription of the various embodiments, when read together with theaccompanying drawings, in which:

FIG. 1 is a schematic top view of a fluid medicament delivery device inaccordance with one embodiment of the invention;

FIG. 2 is a schematic side view of the fluid medicament delivery deviceof FIG. 1;

FIG. 3 is a schematic diagram of an exemplary infusion devicemicro-fluidic circuit in accordance with one embodiment of theInvention;

FIG. 4 is a schematic bottom view of a patient attachment unit of thefluid medicament delivery device of FIG. 1 with an external housingremoved;

FIG. 5 is a schematic perspective view of a mechanical pump system inaccordance with one embodiment of the invention;

FIG. 6 is a schematic exploded view of the mechanical pump systemdepicted in FIG. 5, in accordance with one embodiment of the Invention;

FIG. 7A is a schematic operational diagram of a mechanical pump system,in accordance with one embodiment of the invention;

FIG. 7B is a graph schematically illustrating the actual measuredreaction force experienced when operating a mechanical pump system withan actuation button through a complete dosing cycle, in accordance withone embodiment of the invention;

FIG. 8A is a schematic partial plan view of a mechanical pump systemwith an actuation button at a rest position, in accordance with oneembodiment of the invention;

FIG. 8B is a schematic partial cutaway view of a cam disk of themechanical pump system depicted in FIG. 8A at the rest position;

FIG. 9A is a schematic partial plan view of a mechanical pump systemwith an actuation button at a fill end position, in accordance with oneembodiment of the invention;

FIG. 9B is a schematic partial cutaway view of a cam disk of themechanical pump system depicted in FIG. 9A at the fill end position;

FIG. 10A is a schematic partial plan view of a mechanical pump systemwith an actuation button approaching a point of no return, in accordancewith one embodiment of the invention;

FIG. 10B is a schematic partial cutaway view of a cam disk of themechanical pump system depicted in FIG. 10A approaching the point of noreturn;

FIG. 11A is a schematic partial plan view of a mechanical pump systemwith an actuation button past the point of no return, in accordance withone embodiment of the invention;

FIG. 11B is a schematic partial cutaway view of a cam disk of themechanical pump system depicted in FIG. 11A past the point of no return.

FIG. 12A is a schematic partial plan view of a mechanical pump systemwith an actuation button just before a reengagement position, inaccordance with one embodiment of the invention;

FIG. 12B is a schematic partial cutaway view of a cam disk of themechanical pump system depicted in FIG. 12A just before the reengagementposition;

FIG. 13A is a schematic partial plan view of a mechanical pump systemwith an actuation button past the reengagement position, in accordancewith one embodiment of the invention;

FIG. 13B is a schematic partial cutaway view of a cam disk of themechanical pump system depicted in FIG. 13A past the reengagementposition;

FIG. 14 is a schematic sectional view of a valve with a fluidic outletof a mechanical pump system, in accordance with one embodiment of theinvention;

FIG. 15A1 is a schematic partial plan view of a mechanical pump systemwith an actuation button approaching a point of no return and aninterlock, in accordance with one embodiment of the invention;

FIG. 15A2 is a schematic partial cutaway view of a cam disk of themechanical pump system depicted in FIG. 15A1 approaching the point of noreturn;

FIG. 15B is a schematic enlarged view of the interlock of the mechanicalpump system depicted in FIG. 15A1;

FIG. 16A1 is a schematic partial plan view of a mechanical pump systemwith an actuation button past the point of no return and an interlock,in accordance with one embodiment of the invention;

FIG. 16A2 is a schematic partial cutaway view of a cam disk of themechanical pump system depicted in FIG. 16A1 past the point of noreturn;

FIG. 16B is a schematic enlarged view of the interlock of the mechanicalpump system depicted in FIG. 16A1;

FIG. 17A is a schematic partial plan view of a mechanical pump systemwith an actuation button approaching a point of no return, an interlock,and a switch, in accordance with one embodiment of the invention;

FIG. 17B is a schematic partial plan view of the mechanical pump systemof FIG. 17A after delivering a dose and returning the actuation buttonto a rest position;

FIG. 18A is a schematic partial plan view of a mechanical pump systemwith an actuation button approaching a point of no return, an interlock,and an impulse mechanism, in accordance with one embodiment of theinvention; and

FIG. 18B is a schematic partial plan view of the mechanical pump systemof FIG. 18A immediately after delivering a dose.

DETAILED DESCRIPTION

FIGS. 1 and 2 depict an embodiment of an assembled fluid medicamentdelivery device 100 having at least two modules, a patient attachmentunit 110 and a separate indicator unit 120, each having a housing 110 a,120 a, respectively. As will readily be appreciated, the invention isnot limited in this respect, but is being presented in this two moduledevice for purposes of explanation only. For additional detail on thistype of system see, for example, U.S. patent application Ser. No.12/542,808, filed Aug. 18, 2009, the disclosure of which is herebyincorporated by reference herein in its entirety. The invention hasapplications across a wide variety of fluidic medicament deliverydevices. The depicted fluid medicament delivery device 100, whenassembled, defines a substantially oval shape, although other shapes(circular, oblong, elliptical, etc.) are also contemplated. In general,an assembled device having round corners, smooth edges, etc., may bedesirable, since the device is designed to be worn on the skin of apatient, underneath clothing. Other aspects of the device that make itgenerally unobtrusive during wear include a small size (only aboutseveral inches across) and a low profile. Other device shapes and sizesare also contemplated.

The patient attachment unit 110 includes a bolus button (or actuationelement) 268 for delivering a dose of fluid medicament, as describedbelow. A cannula insertion device is used to insert a cannula throughthe device 110, subcutaneously through the skin S of a patient. Cannulainsertion devices are described in U.S. patent application Ser. No.12/250,760, filed Oct. 14, 2008, the disclosure of which is herebyincorporated by reference herein in its entirety. After insertion, thecannula insertion device is disconnected from the patient attachmentunit 110, and a cap 112 is used to seal the opening to prevent ingressof contaminants, moisture, etc. The separate indicator unit 120 includesan indicator button 122. A textured edge 124, may be present along allor part of the edge of the housing 120 a to provide a gripping surfaceduring attachment and/or disconnection of the indicator unit 120 fromthe patient attachment unit 110. Alternatively or additionally, the edgeof patient attachment unit housing 110 a may also be textured.

The patient attachment unit 110 is connected to and in communicationwith the separate indicator unit 120. The housings 110 a, 120 b of thepatient attachment unit 110 and the indicator unit 120 meet at a curvedinterface 114. Interfaces having other mating shapes are alsocontemplated. The bottom surface of the patient attachment unit 110includes a patient attachment interface 116. The patient attachmentinterface 116 may include one or more adhesive pads secured to thebottom surface of the patient attachment unit 110 for adhering the fluidmedicament delivery device 100 to the skin S of a patient during use.The interface 116 may be any suitable configuration to adhere reliablythe patient attachment unit 110 to the skin S. In one embodiment, theinterface 116 includes a plurality of discrete points of attachment.Other embodiments utilize concentric adhesive circles or ovals.

The indicator button 122 may be used by the patient to test thefunctioning of the fluid medicament delivery device 100, to cancel anotification presently being delivered, or to prompt for a repetition ofa previous message or other information stored by the indicator unit.Actuating the indicator button 122 may initiate one or more tests toindicate to the patient various operational or therapy states of thedevice 100, such as whether the separate indicator unit 120 is properlymounted to the patient attachment unit 110, whether an internal batteryhas sufficient power for continued use, and/or whether pressure sensingwithin the device 110 is operating properly. Other tests are alsocontemplated. A single indicator button 122 may be used to run one ormore tests. The medicament delivery device 100 may be programmed torecognize patterns of actuations of the indicator button to initiatecertain test routines. That is, two actuations in quick succession mayinitiate a “Battery Power Available” test routine, three actuations inquick succession may initiate a “Pressure Sensor Check” test routine,etc. Other combinations of short actuations and long actuations (e.g.,Short, Long, Short; Long, Long, Short, etc.) are also contemplated toinitiate any number of test routines. Alternatively or additionally, twoor more buttons or other input features may be included on the device,for initiating one or more separate tests. Positive or negative feedbackof the test results may be provided to the patient in the form ofaudible sounds of differing tones or durations,illumination/delumination of lights, vibrations, and combinationsthereof. In certain embodiments, light emitting diodes (LEDs) may beused to illuminate the button itself or may illuminate portions of theindicator unit housing to provide feedback to the patient. Graphicalindicia or alphanumeric information may be displayed on a suitableoutput device.

FIG. 3 is a schematic diagram of an exemplary infusion devicemicro-fluidic circuit 250 that may be incorporated into the fluidmedicament delivery device 100 described herein. Other infusion deviceshaving micro-fluidic circuits are described in U.S. Patent ApplicationPublication No. 2005/0165384, published Jul. 28, 2005, the disclosure ofwhich is hereby incorporated by reference herein in its entirety. Themicro-fluidic circuit 250 includes a pressurized or replenishmentreservoir 252 that is, in this case, an elastomer bladder.Alternatively, a flexible vessel or bag compressed by a spring orexternal pressure or force may be utilized. A fill port 254 is used tointroduce fluid, such as insulin, to the micro-fluidic circuit 250. Inthis micro-fluidic circuit 250, introducing insulin via the fill port254 fills both the reservoir 252 and a variable-volume bolus reservoir256. Check valves 258 prevent backflow of insulin in a number oflocations.

During use, insulin is forced from the reservoir 252 by elasticcontraction of the elastomer, through a filter 260, and into twoparallel flowpaths, a basal flowpath 262 and a bolus flowpath 264. Thebasal flowpath 262 delivers a constant dose or steady-state level ofinsulin to a patient; the bolus flowpath 264 delivers a bolus dose ofinsulin to the patient as needed or desired by the patient, for example,in conjunction with a meal. The basal flowpath 262 includes a firstpressure sensor 266A or other pressure or flow sensors in communicationwith the flowpath 262, for example, at a mid-point in the basalflowpath. In an alternative embodiment, the first pressure sensor 266Aor first sensing element may be placed further upstream or downstream inthe basal flowpath, as desired. In another alternative embodiment, aplurality of pressure sensors in communication with the basal flowpath262 may be utilized. A second pressure sensor 266B or second sensingelement is exposed to ambient air pressure P. The function of andrelationship between the pressure sensors 266A, 266B is described inmore detail in the patent application referred to above (i.e. U.S.patent application Ser. No. 12/542,808). In one embodiment, the pressuresensors 266A, 266B consist of micro-electronic-mechanical system (MEMS)sensors. Each MEMS sensor is about 2 mm square, but sensors havingdifferent dimensions may also be used. Both MEMS sensors are containedwithin the indicator unit 120. In FIG. 3, the pressure sensor 266Acommunicates with a portion of the basal circuit 262 between two flowrestrictors 274A, 274B (e.g., microcapillaries). In one embodiment, thisportion between the flow restrictors 274A, 274B may be a pressure sensorchamber. The pressure sensor 266A senses pressure changes in the basalflowpath 262, which may be indicative of occlusion conditions thatincrease pressure therein. The pressure sensor 266B senses changes inambient air pressure external to the fluid medicament delivery device100. The pressure sensors 266A, 266B are absolute pressure sensors, buta single relative pressure sensor may also be utilized. A relativepressure sensor, e.g., a gauge MEMS sensor, may be used to replace bothabsolute pressure sensors.

To deliver a bolus via the bolus flowpath 264, the patient presses abutton (or other actuation element) 268 that drives a single stroke of abolus piston 420 in a displacement or piston chamber 270 and moves a3-way slide valve 456 to deliver a single bolus dose. The valve 456 isconfigured to provide a redundant sealing system for safety purposes, asdescribed in greater detail below. An optional flow restrictor 274Cregulates, in part, the fluid flow through the bolus flowpath 264. Theparallel flowpaths 262, 264 join at a common channel or dosing conduit276 upstream of an internal chamber or a cannula void 278. The cannulavoid 278 is formed in a cannula base 280, which allows a point ofconnection to a cannula 282. The cannula 282 extends below the skin S ofa patient, thus delivering the insulin subcutaneously. In oneembodiment, the actuation of the bolus button 268 may be sensed by theindicator unit 120 with, for example, a magnetic sensor, a Hall effectsensor, or a switch. In an alternative embodiment of the presentinvention, at least one pressure sensor may be placed in the bolusflowpath 264, thereby allowing the indicator unit 120 to sense theactuation of the bolus button 268. Other alternative sensing andsignaling embodiments are discussed below. Conduits 284 having diameterslarger than those of the flow restrictors 274A, 274B, 274C connect thevarious components, generally in serial flow relation.

FIG. 4 depicts a bottom view of the patient attachment unit 110 showingthe internal components and structures therein, with the housingremoved. Specifically, the bottom portion of the housing 110 a, to whichthe attachment interface 116 is secured, has been removed. Theseinternal components and structures correspond generally to themicro-fluidic circuit 250 discussed in FIG. 3. The components andstructures in the patient attachment unit 110 may be disposed in orconnected to a flow manifold 300, which serves as a mounting platformfor the various components. Note that not all conduits and flowcomponents are depicted in FIG. 4, as some components may be secured tothe opposite side of the manifold 300 or formed therein.

As described above with regard to FIG. 3, insulin in the bolus flowpath264 (the bolus flowpath 264, in FIG. 4, is downstream of the labeledarrow) of the micro-fluidic circuit 250 is delivered from the elastomerreservoir 252, filtered through the filter 260, and stored in thevariable-volume bolus reservoir 256. In certain embodiments, theelastomer reservoir 252 may have a total volume of about 3200microliters. The variable-volume bolus reservoir 256 may have a totalvolume of about 180 microliters to about 260 microliters. Other volumesof the various components are also contemplated. When the fluid pressurein the elastomer reservoir 252 is greater than the fluid pressure in thevariable-volume reservoir 256, the variable-volume reservoir 256 willcontinue to fill, subject to the flow rate dictated at least by flowrestrictor 274C in the bolus flowpath 264. Downstream of thevariable-volume bolus reservoir 256 is the bolus displacement pistonchamber 270, which may store a single dose of insulin (e.g., about 5,about 10, about 20, about 25, or greater than about 25 microliters ofinsulin, in various embodiments).

Actuating the bolus button 268 shifts the valve 456 (See FIG. 3) tofluidically couple the piston chamber 270 with the dosing conduit 276and empties the entire contents of the bolus displacement piston chamber270, as described in greater detail below. A check valve 258 allows forfree flow of insulin from the valve 456 to the dosing conduit 276. Thecheck valve 258 prevents backflow during a bolus stroke (i.e., actuationof the bolus button 268) to deliver the single bolus dose. Audible,visual, and/or tactile feedback may be provided to the patient to signalthat a bolus has been delivered. Releasing the bolus button 268 resetsthe valve 456 to fluidically couple the piston chamber 270 to thevariable-volume bolus reservoir 256. The displacement piston chamber 270is then refilled with insulin from the variable-volume bolus reservoir256, which is, in turn, filled with insulin from the reservoir 252. Thebolus flow rate is controlled with a fixed volume-per-stroke of bolusstimulus, i.e., a predetermined volume of insulin-per-stroke. In anotherembodiment, the bolus flow control rate also may be controlled by abolus rate flow restrictor. Also, downstream of the filter 260 is thebasal flowpath 262 (the basal flowpath 262, in FIG. 4, is downstream ofthe labeled arrow) of the micro-fluidic circuit 250. The flowrestrictors 274A, 274B are located on opposite sides of a pressuresensor chamber 302.

In various embodiments, each flow restrictor 274A, 274B has a length ina range of about 18 mm to about 35 mm. Other lengths of the flowrestrictors are also contemplated, for example, from about 10 mm toabout 20 mm. The various channels 284 in the manifold 300 may be formedby, for example, laser cutting, and the flow restrictors 274A, 274B maybe placed therein. The flow restrictors 274A, 274B may be glued or fusedinto the channels, though other methods of retention are alsocontemplated. Exemplary flow restrictors are described in U.S. PatentApplication Publication No. 2006/0054230, the disclosure of which ishereby incorporated by reference herein in its entirety. The flowrestrictors 274A, 274B are connected to and in fluidic communicationwith a pressure sensor chamber 302.

In order to ensure safe reliable operation and prevent delivery ofpartial doses, in one particular embodiment of the bolus circuit, amanually driven mechanical pump system 400 is used, as depicted in FIG.5. The mechanical pump system 400 includes the bolus button actuationelement 268, a direct drive piston system 404, and a lost motion valvesystem 406. The mechanical pump system 400 may also include a signalingdevice, shown schematically at 407, and may be mounted on a base 408.

FIG. 6 depicts the mechanical pump system 400 of FIG. 5 in an explodedview. In one embodiment, the actuation element 268 is substantiallyrectangular with a hollow interior. Alternate shapes are contemplated.An end surface of the actuation element 268 may be configured as a pushbutton for simple manual operation. The actuation element 268 formsvalve contacts 410 a, 410 b at opposite ends within the hollow interior.A return spring (or valve spring) 412 is disposed about the valvecontact 410 a. A rack 414 for mating with a pinion gear 415 (togetherforming a rack and pinion gear system) is disposed on an exterior sidewall of the actuation element 268. When the mechanical pump system 400is assembled, the actuation element 402 substantially surrounds a valvechamber 416 of the lost motion valve system 406 (described in greaterdetail below). The actuation element 268 is in sliding contact with thebase 408 and may be guided by a pair of actuation element guides 418 orother suitable structure to ensure smooth, sliding action during manualactuation and spring return.

The direct drive piston system 404 includes the piston chamber 270, thepiston 420, and a direct drive 422 for moving the piston 420. The pistonchamber 270 is fluidically coupled to the valve chamber 416 via a pistonchamber inlet/outlet 423 (shown in FIG. 8A). The piston chamber 270 isconfigured to slidably house the piston 420. One end of the pistonchamber 270 may be substantially open to allow for a portion of thepiston 420 to travel into and out of the piston chamber 270. The pistonchamber 270 and the piston 420 may be substantially cylindrical, or anyother complementary shape which allows for slidable contact. The piston420 has at least one seal to sealingly engage sidewalls of the pistonchamber 270 so that fluid may not pass beyond the seal. The depictedembodiment has a pair of seals, 424 a and 424 b. A piston spring (orpump spring) 426 is coupled to the piston 420 and a piston retainer 428.The piston retainer 428 is in a fixed position, mounted on supports 430on the base 408. As the piston retainer 428 is fixed, the piston spring426 is configured to constantly bias the piston 420 into the pistonchamber 270 to empty the chamber 270.

The direct drive 422 includes the rack 414 and the gear 415 (the rackand gear system), a drive shaft 432, a ratchet 434, a cam disk 436 and afollower 438 (a cam and follower system), a piston bar 440, and pistonbar guides 442 a, 442 b. A support structure 444 may be provided tosupport the drive shaft 432 and provide smooth, reliable operation ofthe direct drive 422.

The pinion gear 415 is configured to mate with the rack 414, such thatteeth on each are sized and positioned accordingly to allow for apredetermined range of piston travel. The gear 415 may be formedintegrally with the drive shad 432. The drive shaft 432 is mounted tothe base 408, but allowed to rotate relative thereto. While the driveshaft 432 may be substantially round, an upper portion may be apolygonal shape, such as a square or a triangle, to securely engage acorresponding shape on the ratchet 434 to prevent slip. Because of thisconfiguration, movement of the ratchet 434 is directly linked tomovement of the actuation element 268 through the rack and gear system.The ratchet 434 may include four curved ratchet arms 435, each spacedequidistantly about a central circular perimeter and configured forengaging four ledges 446 of the cam disk 436. When configured in thismanner, each full stroke actuation of the bolus button 268 causes aninety degree rotation of the cam disk 436.

In one embodiment, the ratchet 434 mates with an upper surface of thecam disk 436. The upper surface of the earn disk 436 includes the fourledges 446, each configured for engagement with a respective ratchet arm435 to allow for simultaneous engagement during clockwise rotation.However, the ratchet 434 does not drive movement of the cam disk 436when the ratchet 434 is moved in a counter-clockwise direction, allowingeach ratchet arm 435 to eventually reengage a different ledge 446. Thisprocess is described in greater detail below.

A bottom surface of the cam disk 436 may form a track 448, as depictedin FIG. 8B. The track 448 includes four identical sectors, eachoccupying a quarter of the bottom surface of the cam disk 436. Eachsegment includes three distinct sections: a first section of decreasingradius 450, a second section of substantially constant radius 452 (e.g.,slightly decreasing radius), and a third section of steeply increasingradius 454. The track 448 is configured to slidingly interface with anddrive the follower 438, which may be a pin formed integrally with ormounted to the piston bar 440. As the track 448 rotates, the pin 438translates horizontally relative to the center of the cam disk 436. Thepin 438 follows the track 448 and constrains the motion of the pistonbar 440 to the rotation of the cam disk 436.

The piston bar 440 includes the pin 438 on one end and an opening 441for straddling the piston chamber 270 and mating with the piston 420 atthe opposite end. The piston bar 440 is dimensioned so that, for allpoints of travel, the seals 424 a, 424 b on the piston 420 remain withinthe piston chamber 270. The piston bar 440 may also form an opening(e.g., slot 443) so that the piston bar 440 substantially straddles thedrive shall 432. In one embodiment, the piston bar 440 is substantiallyrectangular, however any shape suitable for integrating with the othercomponents may be used. The piston bar guides 442 a, 442 b areconfigured to provide smooth sliding surfaces for the piston bar 440, aswell as to maintain the orientation of the piston bar 440.

The lost motion valve system 406 includes the valve chamber 416 and thevalve 456 slidingly received therein. The valve chamber 416 isfluidically coupled to the piston chamber 270 via a valve chamberinlet/outlet 458, to the reservoir 256 via a reservoir inlet 460, and tothe dosing conduit 276 via a dosing conduit outlet 462 (the inlets andoutlets are best seen in FIG. 8A). The valve chamber 416 and the valve456 may be cylindrical, or any other complementary shape which allowsfor slidable engagement. The valve 456 includes a pair of seals 424 c,424 d, each located near a midpoint of the value 456, to provide aredundant sealing system. Additional seals are also included near eachend of the valve 456 to prevent fluid from leaking out of the valvechamber 416. The pair of seals 424 c, 424 d of the redundant sealingsystem are always disposed within the valve chamber 416 between thereservoir inlet 460 and the conduit outlet 462, due to the limited axialtravel of the valve 456. The seals 424 c, 424 d provide a fluid-tightinterface between the valve 456 and the valve chamber 416. This is adouble fault condition to prevent leakage between the reservoir 256 andthe dosing conduit 276 in the event of a single seal failure. A ventingport 466 is optionally disposed between the seals 424 of the redundantsealing system for dumping any fluid which leaks into that zone due to asingle or double seal failure (a triple fault condition). The fluid isdumped through a fluidic outlet 467 extending the length of the valve456 with openings at either end that is connected with the venting port466, rather than delivered to the dosing conduit 276 and ultimately thepatient (See FIG. 14). This arrangement provides triple safety againstleakage from the reservoir 256 to the patient, because such a connectionmay only be made after the failure of the two seals 424 c, 424 d and theventing port 466. This arrangement also provides safety againstpotential pressurized air bubbles in the piston chamber 270, sincepressure is equilibrated to ambient when the valve 456 shifts from afill position to a dosing position. As can be appreciated, these safetymeasures make this pump system 400 both safe and effective.

The signaling device 407 includes a link to a sensor or other elementfor indicating when a bolus dose has been delivered. Dosage delivery maybe tracked to allow a user to confirm that the device delivered themedicament as intended. Undercounting deliveries may result in the userthinking a lesser amount of medication has been delivered, leading themto attempt to supply additional doses and creating a potentiallydangerous overdosing situation. In each of the present embodiments, asdescribed below, the signaling device 407 counts every dose delivered. Asignal should correlate to actual dose delivery, and not be generatedwhen a dose is not delivered, for example when the actuation element 268is only partially depressed. In certain embodiments, getting an exactcount may require tight mechanical tolerances. The sensor may sense anyof a number of variables that may indicate when a dose has beendelivered, such as pressure in the dosing conduit 276 or the position ofthe actuation element 268. The signaling device 407 may detect thespecific position, the change in position, the threshold velocity, thechange in velocity, or any other parameter of one of a number ofelements that indicates a bolus dose has been or is about to bedelivered, such as through a mechanical, an optical, a capacitive, apotentiometric, or a magnetic detection scheme. In another embodiment,the signaling device 407 may be triggered based on the detection of twodifferent factors, such as the position of one element and the rate atwhich another element is travelling. For safety purposes, if there isany possibility of an inaccurate count, the signaling device 407 shouldpreferably overcount, rather than undercount, to prevent a user frommistakenly delivering too many doses.

The signaling device 407 may provide a tactile stimulus, an audiblestimulus, a visual stimulus, an electronically detectable signal adaptedto be received by an electronic device, or any combination thereof toindicate to a user that a bolus dose has been delivered. The feedbackmay be active, such as an alarm or flashing light when the dose isdelivered, or passive, such as a counter which detects the electronicsignal and displays the number of doses. The dosage count may be storedin an electronic device and displayed later on demand in order to givethe user or a caregiver the ability to study the dosing profile over aperiod of time (e.g., three days, a week, or longer). In someembodiments where a signal generating device, an electronic receiver,and an intelligent device (i.e., having an electronic circuit andsoftware for decoding and interpreting signals to display a value,light, or some other indicia) for processing the signal are used, thesignal generating device may be passive and placed in a low costdisposable subsystem, while the receiver and the intelligent device areplaced in a reusable wall-to-wall electronic subsystem. The intelligentdevice may include an analog and/or digital electronic circuit toreceive signals, decode signals, process signals, and display and/orstore relevant data. A passive element (such as a magnet, a piece ofmagnetic material, a piece of high electrical permeability material, oran optical reflector) may be placed in the disposable device, while anelectronic pick-up device (such as a coil, a GMR sensor, a reed relay,an inter-digitized capacitor, an optical switch or a regular electronicswitch) may be placed in the reusable electronic subsystem. Preservingthe most costly components in the reusable subsystem can reduce longterm operational costs. Using a wireless signal may remove someobstacles for sending an electronic signal between water-proofsubsystems (sometimes one disposable, one non-disposable), but thecommunicating devices should stay in communicable range duringoperation. Also, in some embodiments, the reusable electronic device mayreduce its power consumption by spending much of its time in an ultralow-power mode (or deep sleep). A signal indicating delivery of a bolusdose may transmit sufficient energy to “wake-up” a micro-controller inthe reusable device, such as approximately 2V, 1 μA for 1 μs or aminimum of approximately 2 pJ of energy.

FIG. 7A depicts schematically one method 500 of operating one embodimentof the mechanical pump system 400, relative to the travel of the bolusbutton 268. The method 500 includes a first step 502 of moving theactuation element or button 268 from, a rest position 600 (i.e., at zeromm of button travel) to a fill end position 602 (i.e., at about three mmof button travel) to fill incrementally the piston chamber 270 withmedicament from the reservoir 256, to load the piston spring 426 byretracting the piston 420 relative to the piston chamber 270, and tobegin loading the valve spring 412. A second step 504 involves movingthe actuation element 268 an additional distance beyond the fill endposition 602 to a point just before a point of no return 604 to shiftthe valve 456 from a fill position to a dosing position and to fullyload the valve spring 412. A third step 506 requires moving theactuation element 268 to an end of travel position just past the pointof no return 604, to force a full dose of medicament out of the pistonchamber 270 to the dosing conduit 276 by decoupling the actuationelement 268 from the piston 420, thereby allowing the piston spring 426to drive the piston 420 to empty the piston chamber 270. A fourth step508 includes releasing the actuation element 268 to allow the actuationelement 268 to move from the end of travel position to a reengagementposition 606 to recouple the actuation element 268 to the piston 420(i.e., by indexing of the ratchet 434 with the cam disk 436), and thento the rest position 600 to shift the valve 456 from the dosing positionto the fill position, due to the action of the valve spring 412. Thisresets the mechanical pump system 400 to the state it was in at thestart of the first step 502 permitting delivery of another full bolusdose, if desired. The mechanical operation of the mechanical pump system400 during its operation 500 is described below in greater detail, withreference to FIGS. 8A-11B. Due to the unique arrangement and cooperationof the components, partial doses cannot be delivered, nor can there bedirect fluidic communication between the bolus reservoir 256 and thedosing conduit 276 potentially resulting in an inadvertent overdosingcondition.

FIG. 7B depicts a graph schematically illustrating the actual measuredreaction force experienced when moving the actuation element 268 througha complete dosing cycle of one embodiment of the device 100. Thereaction force depends upon several variables, including the springconstants and range of compression of the piston spring 426 and thevalve spring 412. The reaction force is also influenced by additionalfactors, such as frictional forces on the valve 456, the piston 420, andthe follower 438, and a varying contact angle between the follower 438and the track 448. Fluidic forces and seal stiction may also come intoplay. These additional factors affect some of the nuances of the forceprofile, though its primary shape is dictated by the reaction forcesprovided by the piston spring 426 and the valve spring 412. In thisembodiment, the piston spring 426 has a greater spring constant than thevalve spring 412 (the valve spring constant is displayed generally asthe slope of the dashed line). Specific values for the reaction forcealong the vertical axis are dependent upon the respective springconstants and other system frictional losses. The numbers along thehorizontal axis representing the position of the actuation element 268are merely exemplary of one embodiment of the invention.

As the actuation element 268 is moved by the user from the rest position600 to the fill end position 602, a required first actuating force F₁increases generally linearly at a relatively high slope against a firstreaction force, which is roughly a combination of the forces generatedby compression of the piston spring 426 and the valve spring 412. Thefirst reaction force peaks at the fill end position 602. As theactuation element 268 moves past the fill end position 602, the pistonspring 426 is maintained in a fixed compressed position by the cam disk436. Further travel of the actuation element 268 is compressing furthersolely the valve spring 412 and also moving the valve 456 from the fillposition to the dosing position. This results in a dip or drop in theforce profile, followed by a second lower magnitude and lower slopedreaction force provided solely by the partially compressed valve spring412 and shifting of the valve 456. Accordingly, applying a secondactuating force F₂ to move the actuation element 268 from the fill endposition 602 to the end of travel position further compresses only thevalve spring 412, resulting in a generally shallower slope. The secondreaction force peaks at the end of travel position of the actuationelement 268, where the valve spring 412 is close to its fully compressedor solid height. In one embodiment, the peak second reaction force, F₂,is less than the peak first reaction force, F₁.

The actuation distance between the fill end position 602 and the pointof no return 604 is typically maintained sufficiently small, and thepeak force F₁ is maintained sufficiently large that a user would beunable to react quickly enough to move the actuation element 268 pastthe fill end position 602 and yet reduce the actuation force enough toprevent the actuation element 268 from moving past the point of noreturn 604. Therefore, a user that moves the actuation element 268 pastthe fill end position 602 will reliably and inevitably also push theactuation element 268 past the point of no return 604 to deliver a fulldose of medicament. The greater the difference between the higher peakfirst reaction force F₁ and the lower peak second reaction force F₂, andthe lesser the actuation distance between the peak forces, the moreinevitable it becomes that the user necessarily moves the actuationelement 268 past the point of no return 604.

FIGS. 8A and 8B depict the mechanical pump system 400 at the start ofthe first step 500. The actuation element 268 is in the rest position600 (shown in FIG. 7 and the valve 456 is in the fill position. A gap Gexists between the valve contact 410 a and the valve 456. This gapallows for the actuation element 268 to move to the fill end position602 to withdraw the piston 420 and fill the chamber 270 with a full dosebefore moving the valve 456. The bolus reservoir 256 and the pistonchamber 270 are fluidically coupled via the reservoir inlet 460, thevalve chamber inlet/outlet 458, and the piston chamber inlet/outlet 423only when the valve 456 is in this fill position. The piston 420 isinitially at a closed end of the piston chamber 270, such that only anegligible amount of medicament may be in the piston chamber 270. Thecam follower pin 438 is in a stable position on the cam track 448, beingdriven by the piston spring 426 to a point at the intersection, of thedecreasing radius section 450 and the increasing radius section 454.

As the actuation element or button 268 is moved by the first actuatingforce F₁ applied by the patient on the button 268 from the rest position600 to the fill end position 602, the rack and gear system rotates thedrive shaft 432 clockwise, thereby rotating the ratchet 434 and forcingthe ratchet arms 435 to engage the ledges 446. Further, the valve spring412 starts to be compressed. Additional movement of the actuationelement 268 rotates the cam disk 436, translating the follower 438 (andby extension the piston bar 440 and the piston 420) in a horizontalplane as the follower 438 moves along the decreasing radius section 450.The piston 420 is retracted relative to the closed end of the pistonchamber 270, creating a pressure drop in the piston chamber 270 andincreasing chamber volume for drawing medicament from the bolusreservoir 256 through the reservoir inlet 460, the valve chamberinlet/outlet 458, and the piston chamber inlet/outlet 423 into thepiston chamber 270. This movement also begins to compress the pistonspring 426. Once the piston 420 is fully retracted, and the pistonchamber 270 contains a full dose of medicament, the gap G between thevalve contact 410 a and the valve 456 is zero, and the follower 438 isat the interface with the constant radius section 452. See FIGS. 9A and9B.

When the follower 438 is in the decreasing radius section 450 or theconstant radius section 452 (i.e., the actuation element 268 has notreached the point of no return 604), each movement of the actuationelement 268, either forwards or backwards, is directly linked to themovement of the piston 420. For example, incrementally moving theactuation element 268 forward will further retract the piston 420 (andcompress the piston spring 426), filling the piston chamber 270 to thelevel of the seal 424 a on the piston 420. If the actuation, element 268is released, so that it returns to the rest position 600 due to theforce of the piston spring 420 and the valve spring 412, the pistonspring 426 incrementally forces the piston 420 to empty the pistonchamber 270, limited by the position of the actuation element 268. Sincethe valve 456 is still in the fill position, any medicament emptied fromthe piston chamber 270 returns to the bolus reservoir 256. Thus, partialdoses cannot be delivered to the dosing conduit 276 or the patient. Ascan be appreciated, controlling the volume of the bolus reservoir 256limits the number of bolus doses that may be delivered in a given timeperiod, and the volume may be limited to contain only a non-injuriousamount of medicament. The volume of the bolus reservoir 256 is afraction of the volume of the pressurized reservoir 252, for example ina range of up to about 5% typically. In one embodiment, due to the lowflow rate between the pressurized reservoir 252 and the bolus reservoir256, sufficient time will pass before another bolus dose can bedelivered by the patient in the event the patient fully drains the bolusreservoir 256. See, for example, U.S. Pat. No. 7,517,335, the disclosureof which is hereby incorporated by reference herein in its entirety. Theflow rate can be customized for a particular user, as the use ofhigh-flow capillaries will allow the bolus reservoir 256 to fill morequickly, and the use of low-flow capillaries will restrict the bolusreservoir 256 to fill mom slowly.

FIGS. 9A and 9B depict the mechanical pump system 400 at the end of thefirst step 502/beginning of the second step 504. The actuation element268 is at the fill end position 602 and the piston chamber 270 is filledwith a full dose, when the valve contact 410 a first comes into contactwith the valve 456. The valve spring 412 is partially compressed,biasing the actuation element toward the rest position 600. The piston420 is fully retracted, thereby fully compressing the piston spring 426.The follower 438 is in the constant radius section 452, where movementof the actuation element 268 rotates the cam disk 436, but the follower438 (and therefore the piston bar 440 and the piston 420) does nottranslate.

As the actuation element 268 is moved by the second actuating force F₂to a point just before the point of no return 604, the actuation element268 further compresses the valve spring 410 and begins to shift thevalve 456 from a fill position to a dosing position. As described above,though the actuation element 268 and the piston 420 are still coupled toeach other, the piston 420 does not translate with movement of theactuation element 268.

FIGS. 10A and 10B depict the mechanical pump system 400 at the end ofthe second step 504/beginning of the third step 506. The actuationelement 268 is at a point just before the point of no return 604. Thevalve 456 has moved into the dosing position, fluidically coupling thepiston chamber 270 to the dosing conduit 276 via the piston chamberinlet/outlet 423, the valve chamber inlet/outlet 458, and the dosingconduit outlet 462. The piston chamber 270 and the dosing conduit 276are only fluidically coupled when the valve 456 is in the dosingposition. The follower 438 is just before the point where the constantradius section 452 meets the increasing radius section 454. This pointcorresponds to the point of no return 604 of the actuation element 268.The piston 420 is still coupled to the actuation element 268, as thefollower 438 is still constrained in the constant radius section 452.Release of the button 268 would shift the valve 456 back to the fillposition and drain the piston chamber 270 back into the bolus reservoir256 under the combined action of the piston spring 426 and the valvespring 412.

FIGS. 11A and 11B depict the mechanical pump system 400 Immediatelyafter the actuation element 268 travels beyond the point of no return604, which is the start of the third step 506. The valve 456 is fully inthe dosing position. The follower 438 is just beyond the constant radiussection 452, where the track 448 is no longer providing resistance tothe piston spring 426. This decouples the piston 420 from the actuationelement 268 and allows the piston spring 426 to release, driving thepiston 420 toward the closed end of the piston chamber 270. The piston420 empties the piston chamber 270 of a full dose of medicament, forcingmedicament into the dosing conduit 276 through the valve 456. Thesignaling device 407 sends one of the previously described signals basedon feedback from a sensor, that may include detecting that the actuationelement 268 traveled beyond the point of no return 604.

In other embodiments, the signaling device 407 may be triggered byalternative means utilizing a rib configured to contact another elementat a predetermined point in the process. The signaling device 407 istriggered every time a rib is contacted. For example, a rib may beplaced on each of the increasing radius sections 454 just beyond thepoint corresponding to the point of no return 604 of the actuationelement 268 when the piston 420 begins to deliver the bolus dose. Thefollower 438 contacts one of the ribs only when a full dose is deliveredas this is the only time the follower 438 enters the increasing radiussections 454 from the constant radius sections 452. In anotherembodiment a rib may be placed on the piston 420 and configured tocontact a corresponding element within the piston chamber 270 wheneverthe piston 420 is either in a fully retracted position, such that thepiston chamber 270 is filled with a bolus dose, or in a fully deployedposition, such that a bolus dose has been delivered from the pistonchamber 270. In yet another embodiment, a rib may be disposed on theactuation element 268 and configured to contact an element at the end ofbutton travel. Another embodiment, utilizing a magnet and a coil, isdescribed below with reference to an interlock mechanism.

As the piston spring 426 releases its stored energy, the piston 420 isdecoupled from the actuation element 268. This is depicted as a dashedline in FIG. 7, indicating that the dosing action is independent of thetravel of the actuation element 268 (i.e., whether the actuation element268 is held in position or released, once the piston 420 is decoupled itwill complete its process of delivering a full dose of medicament). Thecam disk 436 slightly advances such that the ratchet arms 435 are nolonger engaged with the ledges 446, and the follower 438 rests at theinterface of the decreasing radius section 450 and the increasing radiussection 454, at the rest position of the follower 438. The actuationelement 268 is limited to the end of travel position, which prevents theratchet arms 435 from reengaging with the ledges 446 by moving theactuation element 268 forward. The only way to reengage the ratchet 434with the cam disk 436 and reset the device to deliver another full doseis to return the actuation element 268 to the rest position 600. Anycycling of the actuation element 268 from past the point of no return604 and a position Intermediate with the reengagement position 606 failsto deliver additional medicament through the valve 456. Such cycling isincapable of moving the piston 420 as the ratchet 434 is rotatingwithout engaging the cam disk 436 (which constrains the filling motionof the piston 420). Though the valve 456 may move when the actuationelement 268 is cycled in this manner, medicament from the reservoir 256cannot enter the piston chamber 270 because the piston 420 is disposedat the closed end under the force of the piston spring 426. As fluidiccommunication between the bolus reservoir 256 and the dosing conduit 276is precluded, no additional medicament will be delivered until thebutton 268 is released, the pump 400 reset, and the complete cycle 500repeated.

Once a dose has been delivered and the actuation element 268 is at theend of travel position, in standard operation the actuation element 268is returned to the rest position 600. The actuation element 268 may bemoved automatically by the valve spring 412. As the actuation element268 is moving back to the rest position 600, the valve contact 410 bcontacts the valve 456 (shown in FIGS. 12A and 13A) and moves the valve456 front the dosing position to the fill position. The piston spring426 drives the piston 420 at a greater rate of speed than the valvespring 412 moves the valve 456 (via the actuation element 268) to ensurethat a full bolus dose is delivered before the valve 456 shifts from thefill to the dosing position in the event the actuation element 268 isimmediately released once it passes the point of no return 604. Further,for the same reasons as described above with respect to FIG. 7B, a useris unlikely to be able to react quickly enough to move the actuationelement 268 past the fill end position 602 without holding the actuationelement 268 for a sufficient moment of time at the end of travelposition after the piston 420 has delivered the bolus dose. The forcerequired to move the actuation element 268 past the fill end position602 may be approximately 5-15N, and is just under 8N in the embodimentdepicted in FIG. 7B.

In another embodiment, an optional interlocking mechanism 480 isincluded to retain the actuation element 268 beyond the point of noreturn 604 (and thus the valve 456 in the dosing position), onlyreleasing the actuation element 268 to return to the rest position 600once the piston 420 reaches the closed end of the piston chamber 270 andthe full dose has been delivered, as depicted in FIGS. 15A1-18B. In oneembodiment, the interlock 480 includes a resilient cantilevered element482, a detent 484, and a release 486. The resilient element 482 extendsoutwardly from a side of the actuation element 268. One end of theresilient element 482 is attached to the actuation element 268 to act asa hinge, allowing the resilient element 482 to deflect easily toward theactuation element 268 and to return to its non-deflected positionextending away from the actuation element 268. The resilient element 482also optionally includes a magnet 488 at its distal end. The detent 484is fixed to the base 408 and configured to contact the resilient element482. One corner of the detent 484 is chamfered to deflect the resilientelement 482 without binding. The release 486 is attached to the pistonbar 440 and is configured to move along or near a surface of the detent484. Distal ends of the release 486 and the detent 484 substantiallyalign when the piston 420 is at the closed end of the piston chamber270. The distal end of the release 486 may also include a pickup 490,such as a coil, a reed relay, or a GMR sensor.

As the actuation element 268 moves from the fill end position 602 to thepoint of no return 604, the resilient element 482 contacts the chamferededge of the detent 484. The detent 484 deflects the resilient element482 toward the actuation element 268 until the resilient element 482passes the detent 484. Once past the detent 484, the resilient element482 returns to its un-deflected state. Despite the bias of thecompressed valve spring 412, the actuation element 268 may not bereturned to the rest position 600 because of the interference betweenthe resilient element 482 and the detent 484 (see FIGS. 15A2 and 15B).Because the piston 420 is in the retracted position, and the release 486is linked to the piston through the piston bar 440, the resilientelement 482 will not be deflected to pass the detent 484 until thepiston 420 delivers a full dose of medicament. As the actuation element268 passes the point of no return 604, the piston spring 426 forces thepiston 420 to empty fully and quickly the medicament from the pistonchamber 270. As the piston bar 440 reaches its end of travel, therelease 486 moves to the end of the detent 484, deflecting the resilientelement 482 and allowing the actuation element 268 to return to the restposition 600 (see FIGS. 16A and 16B) due to the bias of the valve spring412. The resilient element 482 is prevented from reengaging the backsideof the detent 484 following delivery of a dose because of the locationof the release 486, unless the piston bar 440 is retracted.

The coil 490 may be connected to the signaling device 407 to indicatewhen the coil 490 approaches the magnet 488 following delivery of adose. The signaling device 407 may detect the electrical pulse generatedwhen the magnet 488 and the coil 490 are in close proximity. Thesignaling device 407 may be programmed to differentiate between a high,narrow pulse which would be generated when the piston spring 426releases its energy following decoupling, which necessarily delivers adose of medicament, and a lower, longer pulse which could be generatedby cycling the actuation element 268 after delivery of a dose but priorto reengaging the system. In another embodiment also depicted in FIG.15B, a magnet 489 may be placed on the piston chamber 270 in a locationspaced from the closed end, such that the coil 490 and the magnet 489come into close proximity only when the piston chamber 270 is filled anda dose is about to be delivered. A number of related coil and magnetpositions may be used to detect when the piston frame 440 is in thisposition. In this embodiment, the signaling device 407 may be configuredto require two sequential pulses (first from the proximity of the pistonchamber magnet 489 and the coil 490, and then from the proximity of theresilient element magnet 488 and the coil 490) before signaling that adose has been delivered. This prevents a signal from being deliveredwhen the actuation element 270 is cycled following delivery of a dosebut prior to reengaging the system, and also does not require thesignaling device 407 to analyze the strength and length of theparticular pulse. When a magnet and a pickup are used to deliver apulse, the tolerances must be precise enough to ensure the magnet andthe pickup come into a range of proximity, but this scheme does notnecessarily require extraordinary precision. Water-proof electricalconnections or a limited impedance and voltage range tolerant to bothwet and dry electrical connections may be used to ensure accurate andconsistent transmission of an electrical signal from the disposablesubsystem to the reusable subsystem. Also, flexible, low-friction, or nofriction electrical connections may be used when the magnet and/or thepickup are located on moving parts.

In other embodiments, the signaling device 407 may be triggered bydepressing a switch 492, for example located at the end of travel of theactuation element 268 (as depicted in FIGS. 17A and 17B), though theswitch 492 may also be placed at other locations. The switch 492 may beany of a number of types of switches, such as an OTS switch. The switch492 may be located inside a disposable subsystem with electrical leadsconnecting it to a reusable subsystem. The switch 492 may be made withlow-cost parts and the electrical leads may be connected with waterproofconnections, or the switch may work in an impedance and signal voltagerange tolerant to both wet and dry electrical connections.Alternatively, the switch 492 may be located inside a reusable subsystemwith a waterproof window through which the switch 492 may be activated,adding no additional parts or assembly when the housing is made with2-shot molded parts. The signaling device 407 may be triggered by eitherclosing or opening the switch 492. When the optional resilient element482 and the detent 484 are used, there may be a limited distance, forexample approximately 0.1 mm to 0.2 mm, between the end of the actuationelement 268 and the switch 492 when the resilient element 482 is restingon the detent 484. Because of some of the tight tolerances, a lever-armamplification may be used. To prevent additional signal deliveries fromcycling the actuation element 268 before reengaging the system, anadditional switch 493 may be located near the end of travel of thepiston frame 440. Contacting the piston frame switch 493 may “arm” thesignal, and then activating the actuation element switch 492 woulddeliver (and “disarm”) the signal. No signal would be delivered if thesignal is not “armed.” This avoids false dose counts due to cycling theactuation element 268 without delivery of medicament.

In still other embodiments, the rapid movement of the piston frame 440during the delivery of a dose may generate an impulse which istransferred to a magnet. Two different embodiments are depicted in FIGS.18A and 18B: a first embodiment where a magnet 496 a is mounted on theend of an impulse spring 497 mounted (or formed) on an end of the pistonframe 440; and a second embodiment where a magnet 496 b is mounted on aresilient cantilevered arm 499 attached to (or formed on) the end of thepiston frame 496. In both embodiments, when the piston frame 440 stopsat the end of travel after delivering a dose, the magnet 496 willcontinue moving due to extension of the spring 497 or the magnet 496 bwill continue moving due to bending of the resilient cantilevered arm499 until the magnet(s) come into close proximity with a resistivepickup 498 a, 498 b. The pickup 498 may be any of a number of devicescapable of generating an electrical impulse based on the changingproximity of a permanent magnet, such as a coil, a reed relay, and a GMRsensor. The pickup 498 may be located in a reusable section, while lowcost passive parts (e.g., magnets, pieces of high permittivity material,an interrupter for triggering an optical switch, a lever for triggeringa switch, etc.) may be located in a disposable section. The pickup 498may be calibrated to generate an electrical impulse when the permanentmagnet is in a wide proximity, reducing the need for tight tolerances.Detecting only when the piston frame exceeds a threshold velocity andassociated deceleration (i.e., change in velocity) at end of travelensures that the signaling device 407 is only triggered when a dose isdelivered. False signals and counts are not delivered when cyclingwithout resetting the system, because the piston frame 440 will notreach that threshold velocity until forced by the piston spring 426 todeliver the full dose.

In another embodiment, the cam disk 436 may include ribs 487 (depictedin FIGS. 15A2 and 16A2) on the exterior surface, approximately alignedwith the ledges 446. A sensor, such as an optical or a mechanicalsensor, may detect when the ribs 487 cross the axes 491. This onlyoccurs when the actuation element 268 moves past the point of no return604, delivering a dose and completing the quarter turn advance of thecam disk 436. The ribs 487 on the cam disk 436 do not regresscounter-clockwise across the axes 491, only crossing again on the nextquarter turn of the cam disk 436 (i.e., when a next dose is delivered).

FIGS. 12A and 12B depict the mechanical pump system 400 just before theactuation element 268 reaches the reengagement position 606. As theactuation element 268 moves toward the reengagement position 606, theratchet 434 moves counterclockwise while the cam disk 436 remainsstationary with the follower resting at the intersection of thedecreasing radius section 450 and the increasing radius section 454.When the actuation element 268 is near the reengagement position 606,the ratchet arms 435 are slightly deflected inward by the ledges 446. Asthe actuation element 268 is moved past the reengagement position 606,as depicted in FIGS. 13A and 13B, the ratchet arms 435 return to theirradially extended state, allowing for reengagement with the ledges 446when the ratchet 434 is next moved clockwise. This recouples the motionof the piston 420 with the motion of the actuation element 268. When theactuation element 268 is back in the rest position 600, all of thecomponents of the mechanical pump system 400 are back in their originalposition as depicted in FIGS. 8A and 8B, except for the cam disk 436which is functionally in the same position, but has advanced a quarterturn.

The various components utilized in the device described herein may bemetal, glass, and/or any type of polymer suitable for sterilization anduseful for delivering insulin or other medicaments. Polyurethane,polypropylene, polystyrene, nylon, and others, are contemplated for use,as are stainless steel and other medical-grade metals. Morespecifically, medical-grade plastics may be utilized for the dosingconduit itself, as well as other components that contact or otherwisepenetrate the body of the patient.

The terms and expressions employed herein are used as terms andexpressions of description and not of limitation, and there is nointention, in the use of such terms and expressions, of excluding anyequivalents of the features shown and described or portions thereof. Inaddition, having described certain embodiments of the invention, it willbe apparent to those of ordinary skill in the art that other embodimentsincorporating the concepts disclosed herein may be used withoutdeparting from the spirit and scope of the invention. The compositions,components, and functions can be combined in various combinations andpermutations, to achieve a desired result. For example, all materialsfor components (including materials not necessarily previouslydescribed) that are suitable for the application are considered withinthe scope of the invention. Accordingly, the described embodiments areto be considered in all respects as only illustrative and notrestrictive. Furthermore, the configurations described herein areintended as illustrative and in no way limiting. Similarly, althoughphysical explanations have been provided for explanatory purposes, thereis no intent to be bound by any particular theory or mechanism, or tolimit the claims in accordance therewith.

What is claimed is:
 1. A method of dosing a medicament using amechanical pump system comprising an actuation element, a direct drivepiston system including a piston, and a lost motion valve system, themethod comprising the steps of: moving the actuation element from a restposition to a fill end position to fill incrementally a piston chamberof the piston system with medicament from a reservoir; moving theactuation element an additional distance to a point of no return to movea valve of the valve system from a fill position to a dosing position;and moving the actuation element past the point of no return to force afull dose of medicament out of the piston chamber to a dosing conduit.2. The method of claim 1, wherein moving the actuation element from therest position to the fill end position retracts the piston relative tothe piston chamber.
 3. The method of claim 1, wherein the direct drivepiston system comprises at least one of a rack and gear system and a camand follower system.
 4. The method of claim 3, wherein the direct drivepiston system comprises both the rack and gear system and the cam andfollower system.
 5. The method of claim 1, wherein moving the actuationelement from the rest position to the fill end position does not movethe valve.
 6. The method of claim 1, wherein when the actuation elementis moved past the point of no return, the piston is decoupled from theactuation element and automatically delivers a full dose of medicamentto the dosing conduit.
 7. The method of claim 1 further comprising thestep of returning the actuation element to the rest position afterdosing to reset the mechanical pump system.
 8. The method of claim 7,wherein the actuation element is returned to the rest positionautomatically.
 9. The method of claim 7, wherein the actuation elementpasses through a reengagement position prior to reaching the restposition.
 10. The method of claim 9, wherein cycling of the actuationelement from past the point of no return to a position intermediate withthe reengagement position delivers no additional medicament.
 11. Themethod of claim 7, wherein the valve is moved from the dosing positionto the fill position by the actuation element.
 12. The method of claim1, wherein the valve allows fluidic communication between the reservoirand the piston chamber only when the valve is in the fill position. 13.The method of claim 1, wherein the valve allows fluidic communicationbetween the piston chamber and the dosing conduit only when the valve isin the dosing position.
 14. The method of claim 1, wherein the pistonsystem and the valve system are configured to preclude direct fluidiccommunication from the reservoir to the dosing conduit.
 15. The methodof claim 14, wherein the valve system includes a redundant sealingsystem comprising two sealing elements disposed between the reservoirand the dosing conduit.
 16. The method of claim 15, wherein the valvesystem further comprises a venting port disposed between the two sealingelements for dumping medicament leaked between the two sealing elements.17. The method of claim 1, wherein the reservoir is configured to hold afirst volume of medicament less than a volume of a replenishmentreservoir.
 18. The method of claim 1, wherein the piston system and thevalve system are configured to preclude delivery of a partial dose ofmedicament to the dosing conduit.
 19. The method of claim 18, whereinthe mechanical pump system further comprises an interlock for retainingthe valve in the dosing position until a full dose of medicament isdelivered.
 20. The method of claim 1, wherein cycling the actuationelement between the rest position and a position before the point of noreturn delivers no medicament.
 21. The method of claim 1, wherein theactuation element exerts a first increasing reaction force against anactuating force when filling the piston chamber to the fill end positionand a second lower reaction force when the actuation element moves pastthe fill end position.
 22. The method of claim 1 further comprising thestep of delivering a signal only when the full dose is delivered to thedosing circuit.
 23. The method of claim 22, wherein the signal istriggered by at least one of a mechanical, an optical, a capacitive, apotentiometric, and a magnetic input.
 24. The method of claim 23,wherein the signal is triggered based on detecting at least one of aspecific position, a change in position, a threshold velocity, and achange in velocity of a moving component of the mechanical pump system.25. The method of claim 23, wherein the signal comprises at least one ofa tactile stimulus, an audible stimulus, a visual stimulus, anelectronically detectable signal adapted to be received by an electronicdevice, and combinations thereof. 26.-52. (canceled)